PRECLINICAL SAFETY EVALUATION OF BERBERINE IN COMBINATION WITH GLICLAZIDE

Allopathic drugs are generally prescribed for Diabetes Mellitus (Type-II) patients. As the disease is chronic in nature, it necessitates the use of alternative medicine(s) either to supplement the existing allopathic therapy and/or to reduce the associated side effects with their chronic use. The use of herbal drugs is presumed to be safe option due to fewer side effects. However, evaluation of safety of their combination by scientific validation is very essential. Here we evaluated the safety of routinely used second generation drug Gliclazide along with Berberine (herbal drug). The study was conducted in two dissimilar species, rats, and rabbits. In rats and rabbits, the dose of 100 mg/kg of Berberine and 1 mg/Kg Gliclazide dosed separately produced~30% reduction in blood glucose. When both Berberine and Gliclazide were given in combination at similar doses, reduction in blood glucose was found to be ~60%, suggesting significant pharmacodynamic interaction between them. Also, in the rabbit study, Gliclazide pharmacokinetic parameters were studied. We observed significant changes in the pharmacokinetic parameters of Gliclazide (AUC, half-life, Cmax were increased by ~2 folds and clearance, vs. decreased by ~2-4 folds) in the combined regimen, indicating pharmacokinetic interaction. The studies in rat and rabbits (a rodent and a non-rodent), suggests that the combination (Gliclazide and Berberine) at the tested doses is not safe to be used in clinic.